When particles are entrained or dispersed in a flowing fluid, aggregation of the particles to form larger clumps is typically due to some attraction or adhesion between the particles or the addition of a flocculating agent that aids in attracting and aggregating the particles. Attractive forces between the particles may be ionic or physical entanglement. Some flocculating agents, such as chitosan, may also be directly attractive to the particles and thus form clumps of particles in the fluid medium.
Typically, after the clumps of particles are formed in the fluid medium, a physical filtration process is utilized to separate the aggregated, agglomerated, flocculated or otherwise process-formed particle clumps. If this is a filter separation process, the physical filter media and the clumps of particles that have been separated from the fluid media are typically discarded, thus creating additional waste and increasing costs. Also, with the use of this physical filtration process, the yield of the filtrate is lessened, as some of it is used to saturate the filtering material. Further, as the filter fills up, filtration capacity is reduced, and using such filters requires periodic stopping to remove the filter and obtain the particles trapped thereon.
An example of this type of filtration is the filtering of a bioreactor to separate the cells and cell debris from the expressed products of the cells, such as monoclonal antibodies and recombinant proteins. Many times, this entails the use of a diatomaceous earth (DE) filter. The DE filters become filled quickly with the cellular waste from the bioreactor during the filtration process. This decreases the flux rate, the ability of the filter to trap materials and allow the fluid to pass through the filter, and increases the pressure differential between the material to be filtered and the post-filter material. As a result, some of the product from the bioreactor (monoclonal antibodies and recombinant proteins) is lost, thus decreasing the yield of the bioreactor. Also, any high pressure differential generated by the filter blockage can generate product damage.
Thus, methods are sought where continuous filtration may be carried out with little or no loss of the expressed monoclonal antibodies and recombinant proteins while separating most or all of the cells and cell debris that are in the bioreactor fluid. Such continuous methods would also be useful in other filtration applications such as the filtering of oil from water, components from blood, tailings from water in tailing ponds, and, generally, particles from a fluid stream and immiscible or emulsified fluids from a fluid stream.
Acoustophoresis is the separation of particles and secondary fluids from a primary or host fluid using high intensity acoustic standing waves, and without the use of membranes or physical size exclusion filters. It has been known that high intensity standing waves of sound can exert forces on particles in a fluid when there is a differential in both density and/or compressibility, otherwise known as the acoustic contrast factor. The pressure profile in a standing wave contains areas of local minimum pressure amplitudes at its nodes and local maxima at its anti-nodes. Depending on the density and compressibility of the particles, they will be trapped at the nodes or anti-nodes of the standing wave. Generally, the higher the frequency of the standing wave, the smaller the particles that can be trapped due the pressure of the standing wave.
At the MEMS scale, the conventional acoustophoresis systems rely on using half or quarter wavelength acoustic chambers, which at frequencies of a few megahertz are typically less than a millimeter in thickness, and operate at very slow flow rates (e.g., μL/min). Such systems are not scalable since they benefit from extremely low Reynolds number, laminar flow operation, and require minimal fluid dynamic optimization.
At the macro-scale, planar acoustic standing waves have been used to accomplish this separation process. However, a single planar wave tends to trap the particles or secondary fluid in a manner such that they can only be separated from the primary fluid by turning off the planar standing wave. This does not allow for continuous operation. Also, the amount of power that is needed to generate the acoustic planar standing wave tends to heat the primary fluid through waste energy.
Conventional acoustophoresis devices have thus had limited efficacy due to several factors including heat generation, use of planar standing waves, limits on fluid flow, and the inability to capture different types of materials. It would therefore be desirable to provide systems and methods of generating optimized particle clusters to improve gravity separation and collection efficiency. Improved acoustophoresis devices using improved fluid dynamics would also be desirable, so the acoustophoresis can be a continuous process.